In a chromatography separation process, the effectiveness of the column used is a key parameter. The column is generally filled with a solid product in the form of very fine particles usually having a size within 5 and 100 μm, forming the chromatographic bed. To obtain high effectiveness, the arrangement of the particles inside the column must be as uniform as possible, and empty spaces between the chromatographic bed and the inlet/outlet parts of the column must be avoided. It is known from the prior art to use DAC (Dynamic Axial Compression) columns to ensure that there is a compact bed with no free space between the inlet/outlet distributors and the bed.
Dynamic axial compression columns have a piston or another sliding body driven by a cylinder, actuated, for example, by an independent hydraulic circuit; the sliding body makes it possible to compact the packing in a chamber between this piston and a fixed bottom or removable cover. The sliding body comes into contact with the solid phase so as to maintain a constant mechanical pressure on the bed.
Thus, French Patent Application FR-A-2 219 797 teaches a chromatography apparatus in the form of a column designed to contain a bed of adsorbent material. The apparatus consists of a tube which includes a cover and a body sliding in the tube allowing pressure to be exerted in the tube. The sliding body is a piston having at its head a fluid-permeable porous plate. To obtain the bed intended for chromatography, a suspension of particles of a material capable of constituting an adsorbent bed is introduced into the tube without its cover. The cover is fitted to the tube and then pressure is exerted on the said suspension by means of the piston. The liquid is driven through the porous plates and the said particles are compressed between the piston and the cover. This apparatus makes it possible to achieve, in one embodiment, the chosen bed compression stage and the desired particle compaction when the sliding body has travelled between ⅘ and ⅔ of the height of the column.
However, this apparatus has the drawback of achieving imprecise compaction of the bed, since this is determined simply by the position of the piston along the tube. Moreover, there is a risk of the pressure exerted by the piston being greater than the mechanical stresses that the bed can withstand and contact between the bed and the piston may cause the bed to degrade. Furthermore, this apparatus does not make it possible to take into account the risk of the piston crushing the bed, which may degrade the latter.
European Patent Application EP-A-0 145 578 also discloses a chromatography apparatus comprising a tube, one portion of which is intended to contain an adsorbent bed. This tube has two end walls and a piston sliding longitudinally in the tube. The piston marks, between the two end walls, a separation between a chromatography chamber containing the bed and an enclosure in which pressure is applied so as to displace the piston along the tube. The particular feature of that device is that the fluid contained in the enclosure is the liquid to be chromatographed, diverted from the liquid feed line. One portion of the liquid is diverted to the enclosure via an enclosure line and the other portion of the liquid is carried to the chromatography chamber via a flow line passing through the enclosure and the piston. Once the piston is in equilibrium, the force exerted on the enclosure side on the piston is equal to the sum of the force on the piston caused by the flow in the chamber of the liquid to be chromatographed and of the mechanical force of the bed on the piston.
This apparatus makes it possible, in addition to carrying out the elution step, to define the pressure exerted on the bed.
In a first embodiment, the piston has a constant cross section but the pressure in the flow and enclosure lines is regulated by pressure regulator stops. Thus, the stops may be set so that the difference between the pressure exerted by the flow of the liquid and the pressure exerted by the liquid in the enclosure is adjusted to a setpoint pressure on the bed.
In another embodiment, the pressure in the flow and enclosure lines is the same, but the cross section of the piston differs. The piston is one having two cross sections and it slides in corresponding bores, the smaller cross section A being located on the chromatography chamber side and the larger cross section B on the enclosure side. Because of the difference in area of the faces A and B of the piston, the force exerted at B is greater than the force exerted at A. Thus, it is possible to choose the cross sections of the piston so that the difference between the pressure exerted by the flow of the liquid and the pressure exerted by the liquid in the enclosure is adjusted to a setpoint pressure on the bed.
In fact, the apparatus described in the above document has various drawbacks. It does not make it possible to know the position of the piston along the tube, which may crush the bed. This is particularly serious when there is a risk of the chromatographic bed being mechanically degraded. In addition, since the movements of the chromatographic bed are not monitored and the enclosure is unable to discharge the liquid, this apparatus cannot adapt the pressure exerted on the bed according to the movements of the latter and contact between the bed and the piston may degrade the bed. Moreover, this system cannot be used in SMB (Simulating Moving Bed) or in VARICOL mode. In such configurations, the chromatography apparatuses are mounted in a loop and the liquids injected into the beds alternate. In the apparatus disclosed in EP-A-0 145 578, the same liquid is sent into the bed and into the enclosure, the alternating injection of liquids causing the latter to be mixed.